Dr. Oz, Pain, Hot/Cold Receptors

The production of endorphins in tissues in response to nerve stimulation relieves inflammation and pain. Dr. Oz and the medical community seem to forget that hot and cold receptors in the skin can be readily triggered by natural products in foods, to stimulate the release of endorphins and treat inflammation in nearby tissues.

Hot and Cold Don't Easily Penetrate the Skin
Athletic trainers commonly apply hot and cold packs to avoid swelling and inflammation from injuries, and they are always discussing the virtues of various hot/cold regimens. They ignore the extraordinary efficiency of the circulatory system in regulating tissue temperatures and avoiding temperature changes. They also ignore the fact that chemical "hot and cold" salves and ointments are effective without actually changing the temperature of the skin. The essential observation is that triggering hot and cold sensing nerves is more important than changing the temperature of the damaged tissues.

Common Food Molecules Activate Hot/Cold Nerve Receptors
Peppers are hot, because they contain capsaicin that binds to protein receptors on nerves in the skin, which results in the brain sensation of heat. Camphor and castor oil bind to the same receptors. Menthol binds to corresponding cold receptors. Vicks Vaporub has both menthol and camphor, and therefore stimulates both hot and cold sensors. Vicks is also an effective treatment for tissue inflammation.

Vicks and Castor Oil are Effective Treatments for Pain and Inflammation
A bee sting or a burn on a finger will produce reddening, swelling and pain, that can be quickly alleviated by applying Vicks to the wrist. The hot and cold sensors of the wrist would be stimulated and the returning nerve signals would be generally detected in the whole hand and produce endorphins that would calm the inflammation and sooth the injured finger. In a similar way, an inflamed joint can be treated by topical menthol and castor oil, and lower abdominal discomfort can be alleviated by castor oil applied to the belly.

Tendonitis can be Treated with Peppermint Soap
I have treated a persistent tendonitis in my shoulder by applying Dr. Bronner's Peppermint Soap liberally to my shoulder and waiting a few minutes before continuing my shower. This gentle, persistent treatment produced relief within a week. This was a cure for this persistent inflammation and pain. It also works on joints.

What Dr. Oz needs to communicate is that there are simple ways to stimulate hot/cold receptors that have nothing to do with changing the temperature of deeper tissues, but these treatments are very effective in stimulating general endorphin production that reduces troublesome inflammation and pain. As an addendum, vagal stimulation, i.e. through yoga postures such as shavasana or the Valsalva maneuver, can produce a reduction in general inflammation.

Baldness Cure: Low Dose Naltrexone?

Naltrexone can be used to block opioids and provide the basis for treatment for drug abuse, but in low doses (LDN) it provides a paradoxical increase in natural endorphins that reverses inflammation and provides an effective treatment for autoimmune diseases, e.g. MS.

Receptors
A recent anonymous post brought the role of cannabinoid and opioid receptors in baldness to my attention. The relationship between these receptors, inflammation and autoimmunity is very complex. The heat and cold sensors, which also bind capsaicin and menthol, appear to be mediated by endorphins. Acupuncture also seems to function by similar mechanisms and is inhibited by high dose Naltrexone.

Low Dose Naltrexone
A side effect of high dose Naltrexone (e.g. 50 mg/d) is hair loss. Low dose Naltrexone (e.g. 1 mg/day, taken at night) appears to stimulate hair production and it may reverse the effects of Finasteride, since LDN improves libido.

Endorphin-Suppressed Inflammation
I would expect hair loss to be prevented/reversed by topical treatments that block inflammation and autoimmune attack on hair follicles. Curcumin, from turmeric, blocks NFkB and appears to help hair loss. Capsaicin can block inflammation via endorphin production and also helps hair loss. I would also expect that topical menthol and castor oil would reduce hair loss.

Anti-Inflammatory Diet
The anti-inflammatory diet that I recommend, may not be sufficient to block hair loss, but it may provide a good foundation for other anti-inflammatory treatments. In fact, other topical treatments may not be effective unless chronic, diet-based inflammation is eliminated. It may also be important to reduce oxidative stress by optimizing glutathione and vitamin C.

I would appreciate comments by others who may have experience with LDN and balding.

Cure Acne, Back Pain, Tendonitis, Depression

Remedies Include Vicks Vaporub, Castor Oil and Anti-Inflammatory Diet

Simple anti-inflammatory treatments cure some of the most common health complaints. The big question is why people tolerate the problems rather than applying the readily available remedies.

It seems to me that one reason people don’t simply live anti-inflammatory lives and avoid health problems is that attacking the underlying inflammation by approaches that would have prevented the health problem in the first place, is inadequate for fixing the problem after it becomes established.

Health problems based on inflammation may have many different sources of inflammation. Many dietary deficiencies, for example, contribute to inflammation, so what we eat or don’t eat is a major health risk. Other common contributors to inflammation are dental cavities/infections and inadequate exercise.

Common Symptoms of Chronic Inflammation: Acne, Back Pain, Tendonitis, Depression

I have started to ask casual acquaintances if they have any aches or pains, because eliminating dietary sources of inflammation will be evident in relief of these problems. Common complaints are sore joints and tendons related to repeated use. An example is my barber who complained of pain in all of the tendons used to raise his arms to cut hair. Another friend just had her second child and suffered from shooting pains in the tendons of the arm she used to cradle the youngest when she used the other arm on some task.

Simple Anti-Inflammatory Diet Adjustments Get Quick Results

In many cases, a simple change in diet can lower chronic inflammation enough to provide relief from symptoms. Vitamin D deficiency is probably an underlying source of inflammation of most people in the US. So a simple supplement of 2000-5000 IU per day will have noticeable, anti-inflammatory impact on most people.

I recommended vitamin D and fish oil supplements to a friend suffering from chronic back pain. The back pain persisted, but his acne resolved. He stopped taking the supplements, but after physical therapy relieved the back pain, he returned to the supplements as an acne treatment. Now he has long term relief from all of his pains.

Elimination of Dietary Inflammation May Not Resolve Inflammation Based Health Problems

Health problems that start from aggrevated inflammation, may not be eliminated with resolution of the initial cause. My friend’s back ache, for example, didn’t respond to just elimination of deficiencies in his diet. It seemed that the back problems were self-sustaining. After he did exercises to remove the physical aggravation of his back, lack of dietary inflammation prevented the return of the back ache.

Complex Inflammatory Webs

A student of mine suffers from celiac. This is a complex autoimmune disorder of the intestines that is triggered by wheat gluten and is self-perpetuating. Of interest in this context is that celiacs frequently also have back problems. This indicates that the inflammation of the disease is systemic and impacts other tissues. Clearly, reducing dietary inflammation can go only so far in relieving this complex web of reinforcing sources of inflammation.

Simple Anti-inflammatory Interventions

My friend with tendonitis from holding her child got immediate relief from topical application of castor oil and dietary supplements eliminated the problem. Castor oil and capsaicin react with skin heat-sensing neurons to initiate an anti-inflammatory response in adjacent tissue. In a similar way, menthol acts on cold-sensing neurons and relieves pain by reducing inflammation. Vicks Vaporub is a common commercial source of menthol (other sources are blue Listerine mouthwash and Noxema lotion), which give faster relief than longer lasting castor oil for many connective tissue/joint aches. Exercise is another source of relief for inflammation-based aches and pains.

Health: Combinations of Interventions and an Anti-Inflammatory Diet

Anti-inflammatory drugs, such as aspirin, disrupt the molecular signals that produce inflammation and result in relief from inflammation and pain. The common ailments discussed here respond to anti-inflammatory drugs. Depression was mentioned to point out the psychological dimensions of inflammation. Reproduction/birth is controlled at many points by the processes that we call inflammation and the most inflammatory stage is birth. It is not surprising that disruption of the normally rapid resolution of inflammation following birth leads to postpartum depression. It is surprising that postpartum depression can be relieved by anti-inflammatory drugs.

Fighting Inflammation-Based Diseases

Complex diseases such as allergies, asthma, arthritis, vascular/heart diseases, inflammatory bowel diseases, cancers, etc. are all based on chronic inflammation, but they are also self-reinforcing inflammatory diseases. Cures will require elimination of sources of chronic inflammation, e.g. diet, plus disruption of the disease-supporting inflammation, e.g. food/gut flora-stimulation of inflammation of the bowel.

Fundamental to the cure of all diseases is a supporting anti-inflammatory diet and lifestyle.

There Is More Than Antioxidants

Every time a plant product has an impact on a disease it seems to be attributed to its antioxidant activity. Plant products are active, because they bind to proteins. They bind to lots of different proteins.

Krill oil is a good example. The anti-inflammatory activity of krill oil is due to its omega-3 oil (DHA and EPA) content, but krill oil is more potent than expected. Krill oil also contains a terpene, astaxanthene, that is probably derived from its algae diet. Astaxanthene is labeled as an anti-oxidant, but that is much too easy.

Astaxanthene consists of two flat, hydrophobic paddles, connected by a flexible, hydrophobic chain. Those paddles are important, because of their inability to hydrogen bond with water, i.e. hydrophobicity, and therefore their propensity to get stuck in contact with other hydrophobic surfaces. The list of candidate hydrophobic surfaces includes the obvious smaller aromatic rings (e.g. phenylalanine), indole double rings (e.g. tryptophan), and the less obvious sugars (e.g. galactose), unsaturated lipid/prostaglandins and basic amino acids (lysine and arginine). These are dominant cellular interactions.

The interchangeability of the hydrophobic paddle-binders means that astaxanthene can get its paddles stuck in enzyme or receptor protein active sites that normally bind a wide range of ligands (target small molecules, e.g. enzyme substrates). It is likely, therefore, that astaxanthene has anti-inflammatory activity, because it blocks an inflammatory interaction.

The ubiquity of interactions of terpenoids, based on their general structural properties, also gives these molecules access to cellular cytoplasm. These molecules are too large to diffuse through membranes and if they got half way through, they would be permanently stuck in the membrane. Terpenoids will tend to stick to carrier proteins that have hydrophobic patches or slots. These carriers will transport and internalize terpenoids and other similarly shaped molecules, e.g. steroid hormones.

Metformin, the diabetes drug, is another example of a molecule with a flat, hydrophobic side. It is a stretch to call this an antioxidant, but it is useful for this discussion, since one of my students tested to see it it would stick to a tryptophan in the active site of a classic enzyme, beta-galactosidase. Galactose, in the typical substrate for this enzyme, lactose, will bind to the active site, because of a prominent tryptophan. The shocker is that my student showed that metformin also binds to that same site and competes with lactose. Astaxanthene would also be expected to bind in the same way.

Curcumin is one of the most potent anti-inflammatory compounds and the main ingredient in turmuric, binds to proteins that inhibit the inflammatory transcription factor, NFkB. I would expect astaxanthene to also inhibit NFkB.

Capsaicin is a related molecule that binds to the heat/pain sensor in skin and blocks pain sensation. That is how capsaicin is used as a topical analgesic. Castor oil, ricinoleate, binds to the same sensor and competes with capsaicin and also is an effective pain reliever. Note that ricinoleate is a modified fatty acid that could curl up on the same hydrophobic paddle surface as capsaicin.

The bottom line of this discussion is that if someone tries to convince you that resveratrol, the anti-aging ingredient in wine, is an anti-oxidant, be skeptical. Expect that resveratrol will have numerous interactions with proteins and many of those will not be known.

Lectins - Heat’em and Eat’em

Lectins are proteins common in seeds. They bind to sugars attached in chains to proteins, i.e. glycoproteins, and are displayed on the surfaces of cells that line the gut. Lectins could inhibit digestion of raw beans, but cooking makes them digestible.

Fear of lectins is puzzling. Lectins are proteins that have binding sites on their surfaces for specific single or small sequences of sugars. They are present in seeds to protect the seeds from herbivores.

A seed is mostly food (starch, protein, fat) for the plant embryo that will grow from it. This is also true of a chicken egg and just like the egg, the seed contains defensive proteins to inhibit the growth of bacteria, fungi and egg/seed eaters.

The egg has enzymes to degrade bacterial walls and proteins that bind iron, vitamins, etc. needed by bacteria and humans. Eating many raw eggs can lead to vitamin deficiencies. Boiling the eggs, unravels the defensive proteins and makes them digestible and nutritious.

Seeds block being digested by containing proteins that foul the digestion system of would be devourers. For example, soybeans have trypsin inhibitor that binds to our digestive enzyme and makes eating raw soybeans nonproductive and uncomfortable. Boiling soybean meal to produce a curd, i.e. tofu, agglutinates the denatured soy proteins, including the lectins and washes away the soy trypsin inhibitor. Tofu is free of digestion inhibitors and lectin activity.

It is not an accident that lectins bind to human red blood cells. The sugars displayed on the surface of red blood cells are the blood group antigens. Different sugars on the end of the sugar chains decorating RBCs characterize the A, B and O antigens. These same sugars are present on the surfaces of various bacteria. Immune systems don’t produce antibodies to self antigens, so a person with type A blood produces antibodies only to B antigen sugars it encounters on bacteria. A person who is type AB doesn’t produce antibodies to A or B sugar antigens. There aren’t antibodies to O, because that sugar structure is the basis upon which both A and B are made, and some of the
structure is present on all RBCs. Lectins are specific for A or B or other common bacterial sugar antigens.

I did some modeling to show a lectin with lactose (red and gray) bound to sticky tryptophans (yellow) in two places on the surface. In one case a lysine (blue) is draped on the other side. That shows that sugars bind both to aromatic amino acids and to the hydrophobic arms of basic amino acids.


Some people think that humans and other mammals must be protected from lectins and that this protection is shown in human and cow’s milk in the form of antibodies against lectins. This seems to be a misunderstanding. For example, human antibodies secreted in breast milk are secretory IgAs. These antibodies are glycoproteins, i.e. they are proteins with attached sugar chains. Some lectins will bind to these antibodies, because of the attached sugars. These are not lectin-specific antibodies, but rather glyco-specific lectins. The lectins are binding to the glycoprotein antibodies, not the other way around.

It is possible for people to be allergic to lectins, but this is unlikely. For example, peanut allergies involve proteins other than the peanut lectins.

There are some dangerous lectins. For example, ricin is a very nasty, but effective, toxin produced by the castor plant. Ricin is a lectin, in that it binds very specifically to sugars found on the surface of gut cells of insects and humans. After the ricin binds to surface proteins, it is brought into the cells where it chops up the protein synthesizing machinery. That is a dangerous lectin. It takes very little ricin to kill each cell and only a tiny amount to kill a human. Ricin is a terrorist toxin. Yet oil extracted from castor beans contains so little contaminating ricin that it is safe to eat. [Castor oil is wonderful to apply to aching feet overnight for painfree, luxuriously soft feet in the morning.]

The bottom line is that seed lectins add to the nutrition of cooked beans and grains that have been the foundations for several thriving civilizations. The longest living members of the bean and grain cultures are typically older and more fit than comparable individuals with a modern, inflammatory diet based on omega-6 oils.